THE INFLUENCE OF FOOD AND REPEATED DOSING ON THE BIOAVAILABILITY OF INDOMETHACIN FROM A MULTIPLE-UNITS CONTROLLED-RELEASE FORMULATION

  • 1 January 1984
    • journal article
    • research article
    • Vol. 22  (10) , 557-561
Abstract
A concomitant meal did not affect the extent of indomethacin bioavailability from a multiple-units controlled-release capsule formulation containing enteric-coated pellets, but the presence of food delayed absorption. When a capsule containing 75 mg indomethacin was administered after a 12 h fast, the mean peak drug concentrations in plasma of 2.7 .mu.g/ml .+-. 0.8 SD occurred at a mean time of 4.2 h (range 2-6 h). When this dose was administered with a substantial breakfast, the mean of the peak plasma concentration of 2.2 .mu.g/ml .+-. 1.0 SD occurred at 6.4 h (range 5-12 h). Secondary peak plasma drug concentrations, occurring at .apprx. 14 h after dosing, were more prominent and the times to reach the 2nd peak more variable when the capsules were administered with food. Drug bioavailability after co-administration with food was 91% of that following administration after fasting. When the controlled-release capsule was administered during 3 days in a BID [twice a day] dosage regimen, drug bioavailability was 103% of that from a standard capsule administered QID [4 times a day]. The mean peak level after administration of the last dose of 50 mg as controlled-release capsules was 2.5 .mu.g/ml .+-. 1.1 SD, and the means of peak levels after the penultimate and last doses of 25 mg as standard capsules were 2.0 .mu.g/ml .+-. 0.3 SD and 2.1 .mu.g/ml .+-. 0.7 SD, respectively. The controlled-release capsule formulation was a reliable and reproducible source of indomethacin when administered as repeated doses or with food.